NCT00492544

Immunogenicity and Safety of GSK Biologicals' HPV Vaccine 580299 in Healthy Japanese Females 10-15 Years of Age

Completed Phase 3 Results posted Last updated 4 September 2018

What this trial tests

Phase 3 trial testing Cervarix™ (HPV-16/18 L1 VLP AS04) in Infections, Papillomavirus in 100 participants. Completed in 28 March 2008.

Timeline

2 July 2007

Primary endpoint
28 March 2008

28 March 2008

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	prevention
Enrollment	100
Start date	2 July 2007
Primary completion	28 March 2008
Estimated completion	28 March 2008
Sites	5 locations across Japan

Drugs / interventions tested

• Cervarix™ (HPV-16/18 L1 VLP AS04) — full drug profile →

Conditions studied

• Infections, Papillomavirus — all drugs for Infections, Papillomavirus →

Sponsor

GlaxoSmithKline — full company profile →

Who can join

Adults 10 to 15, female only, with Infections, Papillomavirus. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies Primary · One month post Dose 3 (Month 7)

Seroconversion is defined as the appearance of anti-HPV-16 and/or anti-HPV-18 antibodies (i.e. antibody titer ≥ cut-off value) in the sera of subjects seronegative before vaccination. Cut-off values were 8 enzyme-linked immunosorbent assay units per milliliter (EL.U/mL) for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies.

Anti-HPV-16

Group	Value	95% CI
Cervarix Group	92

Anti-HPV-18

Group	Value	95% CI
Cervarix Group	94

Anti-HPV-16 and Anti-HPV-18 Antibody Titers Primary · Before vaccination (PRE) and one month post Dose 3 (Month 7)

Titers are given as geometric mean titers (GMTs) calculated on all subjects.

Anti-HPV-16 (PRE)

Group	Value	95% CI
Cervarix Group	4.4	4.1 – 4.8

Anti-HPV-16 (Month 7)

Group	Value	95% CI
Cervarix Group	19748.0	17147.7 – 22742.7

Anti-HPV-18 (PRE)

Group	Value	95% CI
Cervarix Group	3.7	3.5 – 3.9

Anti-HPV-18 (Month 7)

Group	Value	95% CI
Cervarix Group	8765.3	7543.8 – 10184.4

Number of Subjects Reporting Solicited Local Symptoms Primary · During the 7-day (Days 0-6) period following each vaccination

Solicited local symptoms assessed include pain, redness and swelling.

Pain

Group	Value	95% CI
Cervarix Group	98

Redness

Group	Value	95% CI
Cervarix Group	85

Swelling

Group	Value	95% CI
Cervarix Group	81

Number of Subjects Reporting Solicited General Symptoms Primary · During the 7-day (Days 0-6) period following each vaccination

Solicited general symptoms assessed include arthralgia, fatigue, fever, gastrointestinal symptoms, headache, myalgia, rash, and urticaria.

Arthralgia

Group	Value	95% CI
Cervarix Group	15

Fatigue

Group	Value	95% CI
Cervarix Group	40

Fever

Group	Value	95% CI
Cervarix Group	10

Gastrointestinal symptoms

Group	Value	95% CI
Cervarix Group	17

Headache

Group	Value	95% CI
Cervarix Group	33

Myalgia

Group	Value	95% CI
Cervarix Group	26

Rash

Group	Value	95% CI
Cervarix Group	5

Urticaria

Group	Value	95% CI
Cervarix Group	3

Number of Subjects Reporting Unsolicited Adverse Events (AE) Secondary · During the 30-day (Days 0-29) period following each vaccination

Unsolicited adverse event= Any adverse event (AE) reported in addition to those solicited during the clinical study. Also any "solicited" symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event.

Group	Value	95% CI
Cervarix Group	63

Number of Subjects Reporting New Onset of Chronic Diseases (NOCDs) and Other Medically Significant Conditions Secondary · From Day 0 up to Month 7

NOCDs assessed include e.g. autoimmune disorders, asthma, type I diabetes. Medically significant conditions assessed include adverse events prompting emergency room visits and physician office visits not related to common illnesses or Serious Adverse Events that are not related to common illnesses.

NOCDs

Group	Value	95% CI
Cervarix Group	0

Medically significant conditions

Group	Value	95% CI
Cervarix Group	18

Number of Subjects Reporting Serious Adverse Events (SAEs) Secondary · From Day 0 up to Month 7

Serious adverse events assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.

Group	Value	95% CI
Cervarix Group	0

Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Parameters Secondary · At Day 0 and Month 7

Abnormalities include values outside (above or below) the normal ranges. Normal ranges: alanine aminotransferase (ALT): 5-35 U/L aspartate aminotransferase (AST): 5-50 U/L basophils: 0-2 % bilirubin total: 0.1-1.1 mg/dL blood urea nitrogen: 0-20 mg/dL creatinine: 0.2-1.2 mg/dL eosinophils: 0-7 % hematocrit: 30-45 % hemoglobin: 10-15 g/dL lymphocytes: 18-50 % monocytes: 1-8 % neutrophils: 42-74 % platelets: 10-60 10E4/microL red blood cells: 350-550 10E4/microL total protein: 6.5-8.6 g/dL white blood cells: 4000-15000 /microL

ALT Above (Day 0)

Group	Value	95% CI
Cervarix Group	2

ALT Below (Day 0)

Group	Value	95% CI
Cervarix Group	0

ALT Above (Month 7)

Group	Value	95% CI
Cervarix Group	1

ALT Below (Month 7)

Group	Value	95% CI
Cervarix Group	0

AST Above (Day 0)

Group	Value	95% CI
Cervarix Group	0

AST Below (Day 0)

Group	Value	95% CI
Cervarix Group	0

AST Above (Month 7)

Group	Value	95% CI
Cervarix Group	1

AST Below (Month 7)

Group	Value	95% CI
Cervarix Group	0

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cervarix Group

Serious: 0/100 (0%)

Deaths: —

Other adverse events (14 terms — click to expand)

Reaction	System	Cervarix Group
Pain	General disorders	—
Redness	General disorders	—
Swelling	General disorders	—
Fatigue	General disorders	—
Headache	General disorders	—
Myalgia	General disorders	—
Nasopharyngitis	Infections and infestations	—
Gastrointestinal symptoms	General disorders	—
Injection site pruritus	General disorders	—
Arthralgia	General disorders	—
Fever	General disorders	—
Injection site warmth	General disorders	—
Abdominal pain	Gastrointestinal disorders	—
Dysmenorrhoea	Reproductive system and breast disorders	—

Data from ClinicalTrials.gov NCT00492544 adverse events section.

Sponsor's own description

Human papillomavirus (HPV) infection has been established as a necessary cause of cervical cancer. GSK Biologicals has developed an HPV vaccine (580299) which targets the 2 most common oncogenic HPV types (HPV-16 and HPV-18), found in approximately 70% of all cervical cancers. In previous trials, the vaccine has been found to be efficacious in the prevention of incident and persistent HPV-16/18 infections and associated cytological abnormalities. HPV vaccination should ideally be performed before onset of sexual activity. Previous studies showed that GSK Biologicals' HPV vaccine 580299 is safe and immunogenic when administered to European, Asian, Latin American and Australian pre-adolescents and adolescents. Here, we aim to assess the immunogenicity and safety of the GSK Biologicals' HPV vaccine 580299 in healthy Japanese pre-adolescent and adolescent female subjects aged 10-15 years. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Pooled analysis of large and long-term safety data from the human papillomavirus-16/18-AS04-adjuvanted vaccine clinical trial programme.
   Angelo MG, David MP, Zima J, Baril L, et al · · 2014 · cited 72× · PMID 24644063 · DOI 10.1002/pds.3554